がん悪性化機構を標的とした創薬開発
がん治療の最大の難関である「がん転移」の機序を明らかにし、それを標的とした革新的創薬開発を目指します。
「がん」は増殖する過程において、発生した臓器・組織にとどまることなく他の部位へ転移することで進行します。
この際、生命維持に重要な臓器へ転移すると死に至ることから、転移を抑制することが「がん」の治療戦略の大きな柱となります。
この転移のプロセスには、「血管新生」と「エクソソーム」が重要な役割を担っています。
がんはその増殖の過程において、酸素や栄養を得るために新たな血管を作り出します（腫瘍内血管新生）。
そしてこの新生血管は、がん細胞に栄養を供給するだけでなく、がん細胞が血液に乗って体の他の部分へ移動するための経路（転移経路）ともなります。
血中のがん細胞は、物理的作用や免疫反応等に耐えながら目的臓器に到達し、血管内から臓器・組織内へ移動し新たな転移巣を形成していきます。
がん細胞が分泌する「エクソソーム」という小さな袋状の物質にはマイクロRNAやタンパクなどが含まれており、このエクソソームをがん細胞周囲の細胞に届けることで、
がん細胞の転移促進に好都合な環境（血管新生、免疫抑制、転移先臓器での転移巣形成促進など）を整えることが近年わかってきました。
我々は、転移能の高いがん細胞と低いがん細胞が分泌するエクソソームの内包物およびエクソソーム表面タンパクの違いに着目し、
転移に関わるマイクロRNAやタンパクの同定を進めています。
さらに、血管の管腔形成というこれまで着目されてこなかった機序を促進する分子メカニズム(MTA1-S100A4相互作用)を明らかにし、
それを標的とすることで血管新生が阻害できることを報告してきました。
これら転移促進に関わる分子を標的とした治療戦略を構築・実証し、革新的な抗がん剤の創薬開発に取り組んでいます。
論文一覧
2025年
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Hepatic Stellate Cells Activated by Cancer Cell-derived AMIGO2-containing Small Extracellular Vesicles Promote Cancer Cell Migration by Producing IL-8.
Runa Izutsu, Mitsuhiko Osaki, Heekyung Seong, Reo Sato, Futoshi Okada
Anticancer research 45(4)
2025-04
DOI:
10.21873/anticanres.17528
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Cancer prevention: past challenges and future directions.
HeeKyung Seong, Runa Izutsu, Mitsuhiko Osaki, Futoshi Okada
Genes and environment : the official journal of the Japanese Environmental Mutagen Society 47(1)
2025-02-27
DOI:
10.1186/s41021-025-00326-y
2024年
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Microcell-mediated chromosome transfer between non-identical human iPSCs
Narumi Uno, Hitomaru Miyamoto, Kyotaro Yamazaki, Masaya Egawa, Hiroaki Kobayashi, Kanako Kazuki, Mitsuhiko Osaki, Teruhiko Suzuki, Shusei Hamamichi, Mitsuo Oshimura, Kazuma Tomizuka, Yasuhiro Kazuki
Molecular Therapy - Nucleic Acids 35(4)
2024-12
DOI:
10.1016/j.omtn.2024.102382
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Generation of Monosomy 21q Human iPS Cells by CRISPR/Cas9‐Mediated Interstitial Megabase Deletion
Masaya Egawa, Narumi Uno, Rina Komazaki, Yusuke Ohkame, Kyotaro Yamazaki, Chihiro Yoshimatsu, Yuki Ishizu, Yusaku Okano, Hitomaru Miyamoto, Mitsuhiko Osaki, Teruhiko Suzuki, Kazuyoshi Hosomichi, Yasunori Aizawa, Yasuhiro Kazuki, Kazuma Tomizuka
Genes to Cells
2024-11-24
DOI:
10.1111/gtc.13184
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Prevention of liver metastasis via the pharmacological suppression of AMIGO2 expression in tumor cells.
HeeKyung Seong, Yusuke Kanda, Runa Izutsu, Jumond P Jehung, Junichi Hamada, Mitsuhiko Osaki, Koji Okamoto, Futoshi Okada
Scientific reports 14(1)
2024-11-15
DOI:
10.1038/s41598-024-71827-z
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AMIGO2 enhances the invasive potential of colorectal cancer by inducing EMT.
Runa Izutsu, Mitsuhiko Osaki, HeeKyung Seong, Sanami Ogata, Reo Sato, Jun-Ichi Hamada, Futoshi Okada
Cancer gene therapy
2024-10-08
DOI:
10.1038/s41417-024-00842-z
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AMIGO2 is involved in the spread of peritoneal metastasis in serous ovarian cancer via promoting adhesion to the peritoneal mesothelial cells
Yuki Iida, Mitsuhiko Osaki, Shinya Sato, Runa Izutsu, HeeKyung Seong, Hiroaki Komatsu, Fuminori Taniguchi, Futoshi Okada
International Journal of Clinical Oncology 29(9)
2024-05-29
DOI:
10.1007/s10147-024-02556-6
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Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis.
Masahiro Makinoya, Kozo Miyatani, Yoshiaki Matsumi, Yu Sakano, Shota Shimizu, Yuji Shishido, Takehiko Hanaki, Kyoichi Kihara, Tomoyuki Matsunaga, Manabu Yamamoto, Naruo Tokuyasu, Shuichi Takano, Teruhisa Sakamoto, Toshimichi Hasegawa, Hiroaki Saito, Yuji Nakayama, Mitsuhiko Osaki, Futoshi Okada, Yoshiyuki Fujiwara
Scientific reports 14(1)
2024-05-02
DOI:
10.1038/s41598-024-60967-x
2023年
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Increased chemokine ligand 26 expression and its involvement in epithelial-mesenchymal transition in the endometrium with adenomyosis.
Ai Ikebuchi, Mitsuhiko Osaki, Ikumi Wada, Hiroki Nagata, Kei Nagira, Yukihiro Azuma, Futoshi Okada, Tasuku Harada, Fuminori Taniguchi
Journal of gynecology obstetrics and human reproduction 52(9)
2023-08-18
DOI:
10.1016/j.jogoh.2023.102645
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Epstein-Barr virus reactivation in peripheral B lymphocytes induces IgM-type thyrotropin receptor autoantibody production in patients with Graves' disease.
Keiko Nagata, Kazuhiko Hayashi, Keisuke Kumata, Yukio Satoh, Mitsuhiko Osaki, Yuji Nakayama, Satoshi Kuwamoto, Yoshinori Ichihara, Tsuyoshi Okura, Kazuhiko Matsuzawa, Junichiro Miake, Shuji Fukata, Takeshi Imamura
Endocrine journal 70(6)
2023-06-28
DOI:
10.1507/endocrj.EJ22-0609
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AMIGO2 expression as a predictor of recurrence in cervical cancer with intermediate risk
Yuki Iida, Mitsuhiko Osaki, Shinya Sato, Runa Izutsu, Heekyung Seong, Masayo Okawa, Daiken Osaku, Hiroaki Komatsu, Fuminori Taniguchi, Futoshi Okada
Molecular and Clinical Oncology 19(1)
2023-05-26
DOI:
10.3892/mco.2023.2652
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Full-length human dystrophin on human artificial chromosome compensates for mouse dystrophin deficiency in a Duchenne muscular dystrophy mouse model
Yosuke Hiramuki, Satoshi Abe, Narumi Uno, Kanako Kazuki, Shuta Takata, Hitomaru Miyamoto, Haruka Takayama, Kayoko Morimoto, Shoko Takehara, Mitsuhiko Osaki, Jun Tanihata, Shin’ichi Takeda, Kazuma Tomizuka, Mitsuo Oshimura, Yasuhiro Kazuki
Scientific Reports 13(1)
2023-03-16
DOI:
10.1038/s41598-023-31481-3
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Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis.
Kosaku Okuda, Kengo Nakahara, Akihiro Ito, Yuta Iijima, Ryosuke Nomura, Ashutosh Kumar, Kana Fujikawa, Kazuya Adachi, Yuki Shimada, Satoshi Fujio, Reina Yamamoto, Nobumasa Takasugi, Kunishige Onuma, Mitsuhiko Osaki, Futoshi Okada, Taichi Ukegawa, Yasuo Takeuchi, Norihisa Yasui, Atsuko Yamashita, Hiroyuki Marusawa, Yosuke Matsushita, Toyomasa Katagiri, Takahiro Shibata, Koji Uchida, Sheng-Yong Niu, Nhi B Lang, Tomohiro Nakamura, Kam Y J Zhang, Stuart A Lipton, Takashi Uehara
Nature communications 14(1)
2023-02-04
DOI:
10.1038/s41467-023-36232-6
2022年
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The impact of AMIGO2 on prognosis and hepatic metastasis in gastric cancer patients
Keisuke Goto, Masaki Morimoto, Mitsuhiko Osaki, Akimitsu Tanio, Runa Izutsu, Yoshiyuki Fujiwara, Futoshi Okada
BMC Cancer 22(1)
2022-12
DOI:
10.1186/s12885-022-09339-0
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Kidney organoid derived from renal tissue stem cells is a useful tool for histopathological assessment of nephrotoxicity in a cisplatin-induced acute renal tubular injury model.
Shota Ueno, Kenji Kokura, Yasushi Kuromi, Mitsuhiko Osaki, Futoshi Okada, Shinji Kitamura, Tetsuya Ohbayashi
Journal of toxicologic pathology 35(4)
2022-10
DOI:
10.1293/tox.2022-0006
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Liver Metastasis Formation Is Defined by AMIGO2 Expression via Adhesion to Hepatic Endothelial Cells in Human Gastric and Colorectal Cancer Cells.
Runa Izutsu, Mitsuhiko Osaki, Jumond P Jehung, Hee Kyung Seong, Futoshi Okada
Pathology, research and practice 237
2022-07-08
DOI:
10.1016/j.prp.2022.154015
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Panel of human cell lines with human/mouse artificial chromosomes.
Narumi Uno, Shuta Takata, Shinya Komoto, Hitomaru Miyamoto, Yuji Nakayama, Mitsuhiko Osaki, Ryota Mayuzumi, Natsumi Miyazaki, Chiaki Hando, Satoshi Abe, Tetsushi Sakuma, Takashi Yamamoto, Teruhiko Suzuki, Yoshihiro Nakajima, Mitsuo Oshimura, Kazuma Tomizuka, Yasuhiro Kazuki
Scientific reports 12(1)
2022-02-22
DOI:
10.1038/s41598-022-06814-3
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AMIGO2 contained in cancer cell-derived extracellular vesicles enhances the adhesion of liver endothelial cells to cancer cells.
Runa Izutsu, Mitsuhiko Osaki, Hideyuki Nemoto, Maho Jingu, Ryo Sasaki, Yusuke Yoshioka, Takahiro Ochiya, Futoshi Okada
Scientific reports 12(1)
2022-01-17
DOI:
10.1038/s41598-021-04662-1
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Prevention of tumor progression in inflammation-related carcinogenesis by anti-inflammatory and anti-mutagenic effects brought about by ingesting fermented brown rice and rice bran with Aspergillus oryzae (FBRA)
Hideyuki Nemoto, Marina Otake, Takahiro Matsumoto, Runa Izutsu, Jumond P. Jehung, Keisuke Goto, Mitsuhiko Osaki, Masafumi Mayama, Masataka Shikanai, Hiroshi Kobayashi, Tetsushi Watanabe, Futoshi Okada
Journal of Functional Foods 88
2022-01
DOI:
10.1016/j.jff.2021.104907
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MTA1, a metastasis‑associated protein, in endothelial cells is an essential molecule for angiogenesis.
Mizuho Ishikawa, Mitsuhiko Osaki, Narumi Uno, Takahito Ohira, Hiroyuki Kugoh, Futoshi Okada
Molecular medicine reports 25(1)
2022-01
DOI:
10.3892/mmr.2021.12527
